This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This highly integrated, multidisciplinary application is focused on developing Japanese Macaque Encephalomyelitis (JME), a disease that occurs spontaneously in Japanese macaques and which mimics multiple sclerosis in humans, as a pathophysiogical and genetic model of MS whose etiology and progression more closely resemble MS in humans than other EAE and viral models in non-human primates and rodents. We aim to use this model to better understand how gamma-herpesviruses trigger MS;whether polymorphisms in gene loci that have been linked to MS in humans also predispose JMs to JME;to evaluate the lesions in both symptomatic and subclincal animals to determine if they model numerous aspects of human MS lesions;and to test if gamma-herpesvirus infection directly influences astrogliosis and the accumulation of factors, such as hyaluronan, that can inhibit remyelination in demyelinated lesions. Our long-term goal is to develop JME as a model for testing immunological and neurobiological process underyling MS, and to use this model in pre-clinical screens of novel agents with the potential to inhibit MS attacks and to promote remyelination and regeneration.